Activation of mitogen-activated protein kinases and p90 ribosomal S6 kinase in failing human hearts with dilated cardiomyopathy.
Activation of mitogen-activated protein kinases and p90 ribosomal S6 kinase in failing human hearts with dilated cardiomyopathy.
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DOI：
10.1016/s0008-6363(01)00438-2
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发表时间：
2002
影响因子：
10.8
通讯作者：
Y. Takeishi;Qunhua Huang;J. Abe;W. Che;Jiing-Dwan Lee;H. Kawakatsu;B. Hoit;B. Berk;R. Walsh
中科院分区：
文献类型：
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作者：
Y. Takeishi;Qunhua Huang;J. Abe;W. Che;Jiing-Dwan Lee;H. Kawakatsu;B. Hoit;B. Berk;R. Walsh
目的：MAP激酶家族的新成员大MAP激酶-1（big MAP kinase-1，BMK 1）最近被发现具有促进细胞生长和抑制细胞凋亡的作用。P90核糖体S6激酶（p90 RSK）是细胞外信号调节激酶（ERK）的重要底物之一，通过磷酸化CREB和Na+/H+交换蛋白调节基因表达。最近，我们已经证明，在豚鼠压力超负荷诱导的肥大心肌中，BMK 1、Src（BMK 1的上游调节因子）和p90 RSK的活性增加。然而，这些激酶在人类hearts.Methods的丰度和活动：除了三个经典的MAP激酶（ERK，p38激酶，和c-Jun NH 2-terminal激酶（JNK）），我们研究了Src，BMK 1，和p90 RSK的蛋白质表达和活性，从扩张型心肌病患者（n=9）的心脏收缩。结果：正常供心和衰竭供心的上述激酶蛋白表达水平无显著性差异，但在正常供心和衰竭供心中，上述激酶蛋白表达水平无显著性差异，而在衰竭供心中，上述激酶蛋白表达水平无显著性差异。心力衰竭组ERK 1/2和p90 RSK活性较对照组明显升高（P<0.01和P <0.03），p38激酶活性较对照组明显降低（P<0.05），JNK活性无明显变化。结论：多种MAP激酶、p90 RSK和Src在扩张型心肌病患者的衰竭心肌中表达差异，可能参与了扩张型心肌病的发病机制。
Objective:A new member of the MAP kinase family, big MAP kinase-1 (BMK1), has been recently identified to promote cell growth and attenuate apoptosis. P90 ribosomal S6 kinase (p90RSK), one of the potentially important substrates of extracellular signal regulated kinase (ERK), regulates gene expression in part via phosphorylation of CREB and the Na+/H+exchanger. Recently, we have demonstrated that the activity of BMK1, Src (the upstream regulator of BMK1) and p90RSK was increased in hypertrophied myocardium induced by pressure-overload in the guinea pig. However, the abundance and activity of these kinases in human hearts are unknown.Methods:In addition to the three classical MAP kinases (ERK, p38 kinase, and c-Jun NH2-terminal kinase (JNK)), we examined the protein expression and activity of Src, BMK1, and p90RSK in explanted hearts from patients with dilated cardiomyopathy (n=9). Normal donor hearts, which were not suitable for transplant for technical reasons, were used as controls (n=5).Results:There were no significant differences in the levels of protein expression of these kinases between normal and failing hearts. ERK1/2 and p90RSK were activated in heart failure compared to control (P<0.01 andP<0.03, respectively), while the activity of p38 kinase was decreased (P<0.05) and the activity of JNK was unchanged in heart failure. By contrast, the activities of Src and BMK1 were significantly reduced in end-stage heart failure compared to normal donor hearts (P<0.05).Conclusion:These data suggest that multiple MAP kinases, p90RSK, and Src are differentially regulated in human failing myocardium of patients with idiopathic dilated cardiomyopathy and may be involved in the pathogenesis of this complex disease.